SARS‐CoV‐2 spike glycoprotein‐reactive T cells can be readily expanded from COVID‐19 vaccinated donors

INTRODUCTION: The COVID‐19 vaccine was designed to provide protection against infection by the severe respiratory coronavirus 2 (SARS‐CoV‐2) and coronavirus disease 2019 (COVID‐19). However, the vaccine's efficacy can be compromised in patients with immunodeficiencies or the vaccine‐induced immunoprotection suppressed by other comorbidity treatments, such as chemotherapy or immunotherapy. To enhance the protective role of the COVID‐19 vaccine, we have investigated a combination of the COVID‐19 vaccination with ex vivo enrichment and large‐scale expansion of SARS‐CoV‐2 spike glycoprotein‐reactive CD4(+) and CD8(+) T cells. METHODS: SARS‐CoV‐2‐unexposed donors were vaccinated with two doses of the BNT162b2 SARS‐CoV‐2 vaccine. The peripheral blood mononuclear cells of the vaccinated donors were cell culture‐enriched with T cells reactive to peptides derived from SARS‐CoV‐2 spike glycoprotein. The enriched cell cultures were large‐scale expanded using the rapid expansion protocol (REP) and the peptide‐reactive T cells were evaluated. RESULTS: We show that vaccination with the SARS‐CoV‐2 spike glycoprotein‐based mRNA COVID‐19 vaccine‐induced humoral response against SARS‐CoV‐2 spike glycoprotein in all tested healthy SARS‐CoV‐2‐unexposed donors. This humoral response was found to correlate with the ability of the donors' PBMCs to become enriched with SARS‐CoV‐2 spike glycoprotein‐reactive CD4(+) and CD8(+) T cells. Using an 11‐day REP, the enriched cell cultures were expanded nearly 1000‐fold, and the proportions of the SARS‐CoV‐2 spike glycoprotein‐reactive T cells increased. CONCLUSION: These findings show for the first time that the combination of the COVID‐19 vaccination and ex vivo T cell large‐scale expansion of SARS‐CoV‐2‐reactive T cells could be a powerful tool for developing T cell‐based adoptive cellular immunotherapy of COVID‐19.